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目的:研究复方赖诺普利片在健康人体内药动学特征。方法:单剂量:空腹口服复方赖诺普利片1片(每片复方赖诺普利片含赖诺普利10mg、氢氯噻嗪12.5mg)。多剂量:多次给药连续9d,每天服药1次,每次1片。采用LC-MS法测定血浆中赖诺普利、氢氯噻嗪的浓度,计算药动学参数,以考察复方赖诺普利片多剂量口服达稳态过程和稳态药动学特征。结果:单剂量口服受试制剂:赖诺普利的tmax为(7.3±1.2)h;Cmax为(42.5±6.8)μg.L-1;t1/2为(8.6±1.8)h;MRT为(20.1±3.0);AUC0-72为(545.1±147.4)ng.h.L-1。氢氯噻嗪的tmax为(2.8±0.7)h;Cmax为(81.6±22.7)μg.L-1;t1/2为(13.7±2.0)h;MRT为(10.4±2.0);AUC0-48为(679.8±280.7)ng.h.L-1。多剂量口服受试制剂:赖诺普利的AUCss为(576.9±124.4)ng.h.L-1,Css-max为(47.7±13.2)μg.L-1,Css-min为(6.2±1.8)μg.L-1,Css-av为(24.0±5.2)μg.L-1,DF为(1.71±0.24),tmax为(7.3±1.1)h,t1/2为(13.1±2.7)h;氢氯噻嗪的AUCss为(731.4±224.9)ng.h.L-1,Css-max为(101.0±31.6)μg.L-1,Css-min为(8.4±3.8)μg.L-1,Css-av为(30.5±9.4)μg.L-1,DF为(3.1±1.2),tmax为(3.0±0.9)h,t1/2为(8.8±1.6)h。结论:复方赖诺普利片主要药动学参数单剂量和多剂量给药差异无显著性,复方赖诺普利片在人体内无蓄积。
Objective: To study the pharmacokinetics of compound lisinopril tablets in healthy volunteers. Methods: A single dose: fasting oral compound lisinopril tablets 1 (each compound lisinopril tablets containing lisinopril 10mg, hydrochlorothiazide 12.5mg). Multiple doses: multiple administration for 9d consecutive days, taking 1 time a day, each one. The concentrations of lisinopril and hydrochlorothiazide in plasma were determined by LC-MS method and the pharmacokinetic parameters were calculated to investigate the oral steady-state process and steady-state pharmacokinetics of the compound lisinopril tablets. Results: The single oral dose of lisinopril had a tmax of (7.3 ± 1.2) h, a Cmax of (42.5 ± 6.8) μg.L-1 and a mean of (8.6 ± 1.8) h of t1 / 2. MRT was ( 20.1 ± 3.0); AUC0-72 was (545.1 ± 147.4) ng.hL-1. The tmax for hydrochlorothiazide was (2.8 ± 0.7) h; the Cmax was (81.6 ± 22.7) μg.L-1; the t1 / 2 was (13.7 ± 2.0) h; the MRT was (10.4 ± 2.0); the AUC0-48 was (679.8 ± 280.7) ng.hL-1. The AUCss for lisinopril was (576.9 ± 124.4) ng.hL-1, the Css-max was (47.7 ± 13.2) μg.L-1, and the Css-min was 6.2 ± 1.8 μg (13 ± 2.7) h for t1-2, (24 ± 5.2) μg.L-1 for C-strain and 1.71 ± 0.24 for DF and (7.3 ± 1.1) AUCss was (731.4 ± 224.9) ng.hL-1, Css-max was (101.0 ± 31.6) μg.L-1, Css-min was (8.4 ± 3.8) μg.L- 9.4) μg.L-1, DF was (3.1 ± 1.2), tmax was (3.0 ± 0.9) h, and t1 / 2 was (8.8 ± 1.6) h. Conclusion: There is no significant difference in the main pharmacokinetic parameters of compound lisinopril tablets between single and multiple doses, and compound lisinopril tablets have no accumulation in the human body.